WO2021092462A1 - Methods, systems, and apparatus for closed-loop neuromodulation - Google Patents

Methods, systems, and apparatus for closed-loop neuromodulation Download PDF

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Publication number
WO2021092462A1
WO2021092462A1 PCT/US2020/059509 US2020059509W WO2021092462A1 WO 2021092462 A1 WO2021092462 A1 WO 2021092462A1 US 2020059509 W US2020059509 W US 2020059509W WO 2021092462 A1 WO2021092462 A1 WO 2021092462A1
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WIPO (PCT)
Prior art keywords
endovascular
carrier
electrode array
subject
implanted
Prior art date
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PCT/US2020/059509
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English (en)
French (fr)
Inventor
Thomas James OXLEY
Nicholas Lachlan Opie
Gil Simon RIND
Original Assignee
Synchron Australia Pty Limited
The University Of Melbourne
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to KR1020227019113A priority Critical patent/KR20230019403A/ko
Priority to EP20884265.8A priority patent/EP4051374A4/en
Priority to JP2022526480A priority patent/JP2023501446A/ja
Priority to CN202080078043.5A priority patent/CN115052657A/zh
Priority to AU2020378095A priority patent/AU2020378095A1/en
Priority to CA3160654A priority patent/CA3160654A1/en
Application filed by Synchron Australia Pty Limited, The University Of Melbourne filed Critical Synchron Australia Pty Limited
Priority to BR112022008720A priority patent/BR112022008720A2/pt
Priority to IL292819A priority patent/IL292819A/en
Priority to PCT/US2020/060780 priority patent/WO2021097448A1/en
Publication of WO2021092462A1 publication Critical patent/WO2021092462A1/en
Priority to US17/398,854 priority patent/US11883671B2/en
Priority to US17/659,381 priority patent/US11672986B2/en

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Definitions

  • This disclosure relates generally to endovascular neuromodulation and, more specifically, to methods, systems, and apparatus for closed-loop endovascular neuromodulation .
  • Vagal nerve stimulation has been successful at decreasing the frequency of seizures for people with medically refractory epilepsy and those whom resection is not a suitable option.
  • Over 100,000 people have been implanted with a vagal nerve stimulation (VNS) system, although the outcome for such treatment is moderate.
  • the responder rate, or the rate of patients who have their seizure frequencies reduced greater than 50%, is only 46.6%, with the median seizure reduction being 52.4%.
  • VNS stimulation parameters are oftentimes open-loop, meaning that stimulation is administered continuously or according to a rigid schedule. Generally, stimulation is applied for around one to five minutes followed by a rest period for around four to ten minutes. Consequently, and due to the large amount of power being delivered, battery depletion is a concern as well as hardware malfunctions. Both require additional surgery for the removal of any implantable units for replacement of the battery or malfunctioning hardware components. Recent studies have also drawn attention to several potential side effects associated with this type of continuous or constant stimulation. See, e.g., Sun FT, Morrell MJ, Wharen RE Jr., Responsive Cortical Stimulation for the Treatment of Epilepsy.
  • Neurotherapeutics 2008 Jan 5(1): 68-74 and Morrell M. Brain, Stimulation for Epilepsy: Can Scheduled or Responsive Neurostimulation Stop Seizures? Current Opinion in Neurology, 2006 Apr; 19(2): 164-8.
  • a method of treating epilepsy comprises detecting, using a first electrode array, an electrophysiological signal of a subject.
  • the first electrode array can be coupled to a first endovascular carrier implanted within the subject.
  • the method can also comprise analyzing the electrophysiological signal using a neuromodulation unit implanted within the subject and electrically coupled to the first electrode array and stimulating an intracorporeal target of the subject using a second electrode array in response to the electrophysiological signal detected.
  • the second electrode array can be electrically coupled to the neuromodulation unit.
  • the second electrode array can be coupled to a second endovascular carrier implanted within part of a bodily vessel superior to a base of a skull of the subject.
  • Stimulating the intracorporeal target can further comprise generating an electrical impulse using a pulse generator electrically coupled to the second electrode array.
  • the pulse generator can be implanted within the subject.
  • Generating the electrical impulse can further comprise increasing a current amplitude of the electrical impulse from 0 mA to up to 10 mA in 0.1 mA steps and increasing a voltage of the electrical impulse from 0 V to up to 10 V in 0.25 V steps.
  • the pulse width of the electrical impulse can be set at between 25 pS to about 600 pS.
  • the frequency of the electrical impulse can be set at between 1 Hz and 400 Hz.
  • the method can also comprise delivering the first endovascular carrier and the second endovascular carrier through a singular delivery catheter prior to detecting the electrophysiological signal of the subject.
  • the method can comprise delivering the first endovascular carrier through a first delivery catheter and delivering the second endovascular carrier through a second delivery catheter prior to detecting the electrophysiological signal of the subject.
  • the method can comprise delivering the first endovascular carrier through a first delivery catheter and delivering the second endovascular carrier through a second delivery catheter extending through the first delivery catheter.
  • the method can further comprise stimulating the intracorporeal target of the subject using the first electrode array.
  • the method can also comprise using the second electrode array to detect or record the electrophysiological signal of the subject.
  • an endovascular neuromodulation system for treating epilepsy and/or other conditions or disorders.
  • the system can comprise a first electrode array configured to detect an electrophysiological signal of a subject.
  • the first electrode array can be coupled to a first endovascular carrier configured to be implanted within the subject.
  • the system can also comprise a second electrode array configured to stimulate an intracorporeal target of the subject.
  • the second electrode array can be coupled to a second endovascular carrier configured to be implanted superior to a base of a skull of the subject.
  • the system can further comprise an implantable neuromodulation unit electrically coupled to the first electrode array and the second electrode array.
  • the neuromodulation unit can be configured to analyze the electrophysiological signal detected by the first electrode array and generate an electrical impulse via a pulse generator to be transmitted to the second electrode array to stimulate the intracorporeal target in response to the electrophysiological signal detected.
  • the first endovascular carrier carrying the first electrode array can be implanted or configured to be implanted within a venous sinus of the subject.
  • the first endovascular carrier can be implanted or configured to be implanted within at least one of a superior sagittal sinus, an inferior sagittal sinus, a sigmoid sinus, a transverse sinus, and a straight sinus of the subject.
  • the first endovascular carrier can be implanted or configured to be implanted within a superficial cerebral vein.
  • the first endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Labbe, a vein of Trolard, a Sylvian vein, and a Rolandic vein.
  • the first endovascular carrier can be implanted or configured to be implanted within a deep cerebral vein.
  • the first endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Rosenthal, a vein of Galen, a superior thalamostriate vein, and an internal cerebral vein.
  • the first endovascular carrier can also be implanted within at least one of a central sulcal vein, a post-central sulcal vein, and a pre-central sulcal vein.
  • the first endovascular carrier can also be implanted or configured to be implanted within a vessel extending through a hippocampus or amygdala of the subject.
  • the intracorporeal target can be part of a vagus nerve of the subject.
  • the second endovascular carrier can be implanted or configured to be implanted within part of an internal jugular vein superior to a jugular foramen of the subject.
  • the second endovascular carrier can be implanted or configured to be implanted within a branch or tributary of the internal jugular vein.
  • the second endovascular carrier can also be implanted within part of an internal carotid artery superior to the base of the skull of the subject.
  • the intracorporeal target can be a cerebellum of the subject.
  • the second endovascular carrier can be implanted or configured to be implanted within at least one of a sigmoid sinus, a transverse sinus, and a straight sinus of the subject.
  • the intracorporeal target can be a motor cortex of the subject.
  • the second endovascular carrier can be implanted or configured to be implanted within at least one of a superior sagittal sinus, an inferior sagittal sinus, a central sulcal vein, a post-central sulcal vein, and a pre-central sulcal vein.
  • the second endovascular carrier can be implanted or configured to be implanted within a superficial cerebral vein.
  • the second endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Labbe, a vein of Trolard, a Sylvian vein, and a Rolandic vein.
  • the second endovascular carrier can also be implanted or configured to be implanted within a deep cerebral vein.
  • the second endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Rosenthal, a vein of Galen, a superior thalamostriate vein, and an internal cerebral vein.
  • the intracorporeal target can be at least one of an anterior nucleus of thalamus, a centromedian nucleus of thalamus, a fornix, a hippocampus, a hypothalamus, a subthalamic nucleus, and a caudal zone incerta.
  • the second endovascular carrier can also be implanted or configured to be implanted within a vessel extending through a hippocampus or amygdala of the subject.
  • the first endovascular carrier carrying the first electrode array and the second endovascular carrier carrying the second electrode array can be implanted in any combination of the bodily vessels disclosed herein.
  • the first endovascular carrier can be implanted within a venous sinus and the second endovascular carrier can be implanted within a superficial cerebral vein.
  • the first endovascular carrier can be implanted within deep cerebral vein and the second endovascular carrier can be implanted within an internal jugular vein.
  • the neuromodulation unit can be implanted or configured to be implanted within the subject.
  • the neuromodulation unit can be implanted or configured to be implanted within a forearm of the subject.
  • the neuromodulation unit can be implanted or configured to be implanted within a pectoral region of the subject.
  • the neuromodulation unit can also be implanted or configured to be implanted within an armpit region of the subject.
  • the first electrode array can be electrically coupled to the neuromodulation unit via a first transmission lead having a first lead diameter.
  • the first transmission lead can extend through a neck of the subject.
  • the first lead diameter can be between about 0.5 mm and 1.5 mm.
  • the second electrode array can be electrically coupled to the neuromodulation unit via a second transmission lead having a second lead diameter.
  • the second transmission lead can extend through a neck of the subject.
  • the second lead diameter can be between about 0.5 mm and 1.5 mm.
  • the first electrode array and the second electrode array can be coupled to the neuromodulation unit via one transmission lead having a lead diameter.
  • the one transmission lead can extend through a neck of the subject.
  • the lead diameter can be between about 0.5 mm and 1.5 mm.
  • the pulse generator can be part of the neuromodulation unit.
  • the pulse generator can be powered and activated by an extracorporeal device.
  • the pulse generator can comprise a first magnetic component and the extracorporeal device can comprise a second magnetic component configured to be magnetically coupled to the first magnetic component.
  • the pulse generator can be configured to be charged by the extracorporeal device via electromagnetic induction when the extracorporeal device is placed in proximity to the pulse generator.
  • the neuromodulation unit can be powered by one or more batteries.
  • the extracorporeal device can be provided as part of an armband when the neuromodulation unit is implanted within an arm of the subject.
  • At least one of the first endovascular carrier and the second endovascular carrier can be an expandable stent or endovascular scaffold comprising an electrode array coupled to the expandable stent or endovascular scaffold.
  • at least one of the first endovascular carrier and the second endovascular carrier can be a self-expandable stent or self-expandable endovascular scaffold.
  • At least one of the first endovascular carrier and the second endovascular carrier can be a wire or cable configured to be wound or coiled comprising an electrode array coupled to the wire or cable. The wire or cable can be wound in a substantially helical pattern.
  • At least one of the first endovascular carrier and the second endovascular carrier can be a wire or cable comprising a sharp distal end for penetrating through lumen or vessel walls.
  • at least one of the first endovascular carrier and the second endovascular carrier can be a wire or cable comprising an anchor.
  • the anchor can be at least one of a barbed anchor and a radially-expandable anchor.
  • the neuromodulation unit can further comprise a telemetry unit.
  • the telemetry unit can be configured to analyze the electrophysiological signal detected by comparing the electrophysiological signal against one or more signal thresholds or patterns.
  • the electrophysiological signal can be a local field potential (LFP) and/or an intracranial/cortical EEG measured within a brain of the subject.
  • the electrophysiological signal can be an electrocorticography signal.
  • the first endovascular carrier, the second endovascular carrier, and/or the transmission lead can be made in part of platinum tungsten, gold, aluminum, Nitinol wire, rhodium, iridium, nickel, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium- nickel-molybdenum alloy, and/or stainless steel.
  • the method can comprise detecting, using a first electrode array, an electrophysiological signal of a subject.
  • the first electrode array can be coupled to an endovascular carrier implanted superior to a base of a skull of the subject.
  • the method can further comprise analyzing the electrophysiological signal using a neuromodulation unit electrically coupled to the first electrode array.
  • the method can also comprise stimulating an intracorporeal target of the subject using a second electrode array in response to the electrophysiological signal detected.
  • the second electrode array can be coupled to the same endovascular carrier.
  • the electrodes of the second electrode array are separate from the electrodes of the first electrode array.
  • the first electrode array and the second electrode array can record or transmit data to the neuromodulation unit via different channels.
  • Stimulating the intracorporeal target can further comprise generating an electrical impulse using a pulse generator electrically coupled to the second electrode array.
  • the pulse generator can be implanted within the subject.
  • Stimulating the intracorporeal target further can comprise generating an electrical impulse using a pulse generator electrically coupled to the second electrode array.
  • Generating the electrical impulse can further comprise increasing a current amplitude of the electrical impulse from 0 mA to up to 10 mA in 0.1 mA steps and increasing a voltage of the electrical impulse from 0 V to up to 10 V in 0.25 V steps.
  • the pulse width of the electrical impulse can be set at between 25 pS to about 600 pS.
  • the frequency of the electrical impulse can be set at between 1 Hz and 400 Hz.
  • the system can comprise a first electrode array configured to detect an electrophysiological signal of a subject.
  • the first electrode array can be coupled to an endovascular carrier configured to be implanted endovascularly superior to the base of the skull of the subject.
  • the system can also comprise a second electrode array configured to stimulate an intracorporeal target of the subject.
  • the second electrode array can be coupled to the same endovascular carrier.
  • the system can further comprise an implantable neuromodulation unit electrically coupled to the first electrode array and the second electrode array.
  • the neuromodulation unit can be configured to analyze the electrophysiological signal detected by the first electrode array and generate an electrical impulse via a pulse generator to be transmitted to the second electrode array to stimulate the intracorporeal target in response to the electrophysiological signal detected.
  • the intracorporeal target can be part of a vagus nerve of the subject.
  • the endovascular carrier can be implanted or configured to be implanted within part of an internal jugular vein superior to a jugular foramen of the subject.
  • the endovascular carrier can be implanted or configured to be implanted within a branch or tributary of the internal jugular vein.
  • the endovascular carrier can be implanted or configured to be implanted within part of an internal carotid artery superior to the base of the skull of the subject.
  • the intracorporeal target can be a cerebellum of the subject.
  • the endovascular carrier can be implanted or configured to be implanted within at least one of a sigmoid sinus, a transverse sinus, and a straight sinus of the subject.
  • the intracorporeal target can be a motor cortex of the subject.
  • the endovascular carrier can be implanted or configured to be implanted within at least one of a superior sagittal sinus, an inferior sagittal sinus, a central sulcal vein, a post-central sulcal vein, and a pre-central sulcal vein.
  • the endovascular carrier can also be implanted within a superficial cerebral vein.
  • the endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Labbe, a vein of Trolard, a Sylvian vein, and a Rolandic vein.
  • the endovascular carrier can be implanted or configured to be implanted within a deep cerebral vein.
  • the endovascular carrier can be implanted or configured to be implanted within at least one of a vein of Rosenthal, a vein of Galen, a superior thalamostriate vein, and an internal cerebral vein.
  • the neuromodulation unit can be implanted or configured to be implanted within the subject.
  • the neuromodulation unit can be implanted or configured to be implanted within a forearm of the subject.
  • the neuromodulation unit can be implanted or configured to be implanted within a pectoral region of the subject.
  • the neuromodulation unit can also be implanted or configured to be implanted within an armpit region of the subject.
  • the first electrode array can be electrically coupled to the neuromodulation unit via a first transmission lead having a first lead diameter.
  • the first transmission lead can extend through a neck of the subject.
  • the first lead diameter can be between about 0.5 mm and 1.5 mm.
  • the second electrode array can be electrically coupled to the neuromodulation unit via a second transmission lead having a second lead diameter.
  • the second transmission lead can extend through a neck of the subject.
  • the second lead diameter can be between about 0.5 mm and 1.5 mm.
  • the first electrode array and the second electrode array can be coupled to the neuromodulation unit via one transmission lead having a lead diameter.
  • the one transmission lead can extend through a neck of the subject.
  • the lead diameter can be between about 0.5 mm and 1.5 mm.
  • the pulse generator can be part of the neuromodulation unit.
  • the pulse generator can be powered and activated by an extracorporeal device.
  • the pulse generator can comprise a first magnetic component and the extracorporeal device can comprise a second magnetic component configured to be magnetically coupled to the first magnetic component.
  • the pulse generator can be configured to be charged by the extracorporeal device via electromagnetic induction when the extracorporeal device is placed in proximity to the pulse generator.
  • the neuromodulation unit can be powered by one or more batteries.
  • the extracorporeal device can be provided as part of an armband when the neuromodulation unit is implanted within an arm of the subject.
  • the endovascular carrier can be an expandable stent or endovascular scaffold comprising an electrode array coupled to the expandable stent or endovascular scaffold.
  • the endovascular carrier can be a self-expandable stent or self-expandable endovascular scaffold.
  • the endovascular carrier can be a wire or cable configured to be wound or coiled comprising an electrode array coupled to the wire or cable.
  • the wire or cable can be wound in a substantially helical pattern.
  • the endovascular carrier can be a wire or cable comprising a sharp distal end for penetrating through lumen or vessel walls.
  • the endovascular carrier can be a wire or cable comprising an anchor.
  • the anchor can be at least one of a barbed anchor and a radially-expandable anchor.
  • the neuromodulation unit can further comprise a telemetry unit.
  • the telemetry unit can be configured to analyze the electrophysiological signal detected by comparing the electrophysiological signal against one or more signal thresholds or patterns.
  • the electrophysiological signal can be a local field potential (LFP) and/or an intracranial/cortical EEG measured within a brain of the subject.
  • the electrophysiological signal can be an electrocorticography signal.
  • the endovascular carrier and/or the transmission lead(s) can be made in part of platinum tungsten, gold, aluminum, Nitinol wire, rhodium, iridium, nickel, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, and/or stainless steel.
  • Fig. 1 illustrates one embodiment of an endovascular neuromodulation system for treating epilepsy and other disorders/conditions.
  • Figs. 2A-2D illustrate various embodiments of endovascular carriers.
  • Fig. 3A illustrates possible implantation sites for components of the neuromodulation system.
  • Fig. 3B illustrates a neuromodulation unit implanted within an arm of a subject.
  • Fig. 4A-4C illustrate one embodiment of a transmission lead used to connect an electrode array to another electrode array or to the neuromodulation unit.
  • Fig. 5A-5C illustrate an example method of implanting an embodiment of an electrode array.
  • Fig. 6 illustrates one embodiment of a method of treating epilepsy.
  • Fig. 7 illustrates another embodiment of a method of treating epilepsy.
  • FIG. 8A illustrates an embodiment of an endovascular carrier implanted within an internal jugular vein of a subject.
  • Fig. 8B illustrates a partial sectional view of a transverse section of a subject at the level of the C6 vertebra showing the vagus nerve and surrounding vessels.
  • Fig. 8C illustrates a proximity of the internal jugular vein to the vagus nerve.
  • Fig. 9A-9G illustrate certain veins and sinuses that can serve as implantation sites for the endovascular carriers.
  • Fig. 10 illustrates one embodiment of a method of deploying or delivering endovascular carriers.
  • FIG. 11 illustrates another embodiment of a method of deploying or delivering the endovascular carriers.
  • FIG. 12 illustrates yet another embodiment of a method of deploying or delivering the endovascular carriers.
  • Fig. 13 illustrates an embodiment of a delivery catheter comprising a bifurcated transmission lead.
  • Fig. 1 illustrates one embodiment of an endovascular neuromodulation system 100 for treating epilepsy and other disorders/conditions.
  • the neuromodulation system 100 can comprise a plurality of electrode arrays 102 electrically coupled to a neuromodulation unit 104 via transmission leads 106 or wires.
  • the neuromodulation system 100 can comprise a first electrode array 102 A and a second electrode array 102B electrically coupled to the neuromodulation unit 104.
  • Each of the electrode arrays 102 can be coupled to an endovascular carrier 108.
  • the first electrode array 102 A can be coupled to a first endovascular carrier 108 A configured to be implanted endovascularly within the subject.
  • the second electrode array 102B can be coupled to a second endovascular carrier 108B configured to be implanted endovascularly within the subject.
  • first endovascular carrier 108A and the second endovascular carrier 108B can be implanted within different vessels (e.g., different veins, arteries, or sinuses) of the subject. In other embodiments, the first endovascular carrier 108A and the second endovascular carrier 108B can be implanted within the same vessel or within different segments of the same vessel.
  • the first electrode array 102 A can be configured to detect or record an electrophysiological signal of a subject and the second electrode array 102B can be configured to stimulate an intracorporeal target (e.g., a target nerve, a target brain region or area, or other target tissue) of the subject.
  • the neuromodulation unit 104 can be configured to analyze the electrophysiological signal detected or recorded by the first electrode array 102A and transmit an electrical impulse to the second electrode array 102B via a pulse generator 110 in response to the electrophysiological signal detected or recorded.
  • the first electrode array 102A and the second electrode array 102B can both be configured to detect or record an electrophysiological signal of the subject.
  • the first electrode array 102 A and the second electrode array 102B can both be configured to stimulate one or more intracorporeal targets of the subject. The intracorporeal target(s) will be discussed in more detail in later sections.
  • the first electrode array 102 A can comprise a plurality of electrodes 112 coupled to the first endovascular carrier 108A.
  • the first electrode array 102A can comprise between 2 and 16 electrodes. In other embodiments, the first electrode array 102A can comprise between 16 and 20 electrodes or more than 20 electrodes.
  • the second electrode array 102B can comprise a plurality of electrodes 112 coupled to the second endovascular carrier 108B.
  • the second electrode array 102B can comprise between 2 and 16 electrodes.
  • the second electrode array 102B can comprise between 16 and 20 electrodes or more than 20 electrodes.
  • the electrode arrays 102 When the electrode arrays 102 (e.g., any of the first electrode array 102A or the second electrode array 102B) are used to detect or record an electrophysiological signal of the subject, the electrode arrays can be referred to as recording electrode arrays. Moreover, when the electrode arrays (e.g., any of the first electrode array 102A or the second electrode array 102B) are used to stimulate an intracorporeal target of the subject, the electrode arrays can be referred to as stimulating electrode arrays.
  • the first endovascular carrier 108A and the second endovascular carrier 108B can be expandable stents or endovascular scaffolds.
  • the endovascular carrier and the electrode arrays coupled to such a carrier can be referred to as a stent-electrode array 109.
  • Stent-electrode arrays 109 will be discussed in more detail in later sections.
  • At least one of the first endovascular carrier 108A and the second endovascular carrier 108B can be a biocompatible coiled wire 200 (see, e.g., Fig. 2A), a biocompatible anchored wire 208 (see, e.g., Fig. 2C), or a combination thereof.
  • the first endovascular carrier 108A can be the same as the second endovascular carrier 108B (e.g., both the first endovascular carrier 108A and the second endovascular carrier 108B can be stent-electrode arrays 109, coiled wires 200, or anchored wires 208).
  • the first endovascular carrier 108A can be different from the second endovascular carrier 108B (e.g., the first endovascular carrier 108A can be a stent-electrode array 109 and the second endovascular carrier 108B can be a coiled wire 200).
  • Fig. 1 illustrates the neuromodulation system 100 comprising two electrode arrays 102 and two endovascular carriers 108
  • the neuromodulation system 100 can comprise between three to five electrode arrays 102 and endovascular carriers 108.
  • the neuromodulation system 100 can comprise between five to ten electrode arrays 102 and endovascular carriers 108.
  • the neuromodulation unit 104 can be configured to be implanted within the subject.
  • the neuromodulation unit 104 can be configured to be implanted within a forearm of the subject (see, e.g., Fig. 3B). In other embodiments, the neuromodulation unit 104 can be configured to be implanted within a pectoral region of the subject (see, e.g., Fig. 3A). The neuromodulation unit 104 can also be implanted or configured to be implanted within an armpit region of the subject.
  • Each of the first electrode array 102 A and the second electrode array 102B can be coupled via one or more transmission leads 106 or lead wires to the neuromodulation unit 104.
  • the transmission leads 106 can be inserted or otherwise coupled to a header portion 114 of the neuromodulation unit 104.
  • the header portion 114 can comprise a different plug receptor for leads or plugs coming from different electrode arrays.
  • the header portion 114 can comprise a 0.9 mm plug receptor for receiving a plug or connector from a first transmission lead 106A connected or coupled to the first electrode array 102 A serving as the recording electrode array and a 1.3 mm plug receptor for receiving a plug or connector from a second transmission lead 106B connected or coupled to the second electrode array 102B serving as the stimulation electrode array.
  • the neuromodulation unit 104 can comprise a unit housing 116.
  • the unit housing 116 can be a hermetically sealed housing or casing such that electronic components within the neuromodulation unit 104 are encapsulated by the unit housing 116.
  • the unit housing 116 can be made of a biocompatible material.
  • the unit housing 116 can be made in part of a metallic material (e.g., titanium, stainless steel, platinum, or a combination thereof), a polymeric material, or a combination thereof.
  • the pulse generator 110 can be part of the neuromodulation unit 104 or contained within the unit housing 116.
  • the implantable neuromodulation unit 104 can comprise one or more batteries (e.g., rechargeable or non- rechargeable batteries).
  • the batteries of the neuromodulation unit 104 can be recharged via wireless inductive charging.
  • the neuromodulation unit 104 can be powered and/or activated by an extracorporeal device 300 (see, for example, Fig. 3A).
  • the neuromodulation unit 104 can comprise a first magnetic component 118 and the extracorporeal device 300 can comprise a second magnetic component 302 (see, for example, Fig. 3A) configured to be magnetically coupled to the first magnetic component 118.
  • the neuromodulation unit 104 including the pulse generator 110, can be configured to be charged by the extracorporeal device 300 via electromagnetic induction or activated by the extracorporeal device 300 when the extracorporeal device 300 is placed in proximity to the neuromodulation unit 104, such as by holding the extracorporeal device 300 close to an implantation site of the neuromodulation unit 104.
  • any reference to the neuromodulation unit 104 can also refer to the pulse generator 110.
  • the pulse generator 110 can be a separate device or apparatus from the neuromodulation unit 104.
  • the pulse generator 110 can be implanted within the subject and the neuromodulation unit 104 can be an extracorporeal unit located and operating outside of the body of the subject.
  • the neuromodulation unit 104 can serve as the extracorporeal device 300 and can process data received wirelessly or via physical leads from the first electrode array 102A, the second electrode array 102B, or a combination thereof.
  • the implantable pulse generator 110 can comprise one or more batteries (e.g., rechargeable or non-rechargeable batteries). In certain embodiments, the batteries of the pulse generator 110 can be recharged via wireless inductive charging.
  • the pulse generator 110 can be powered and activated by the extracorporeal device 300 (see, e.g., Fig. 3).
  • the pulse generator 110 can comprise a first magnetic component 118 and the extracorporeal device 300 can comprise a second magnetic component 302 configured to be magnetically coupled to the first magnetic component 118.
  • the pulse generator 110 can be configured to be charged by the extracorporeal device 300 via electromagnetic induction when the extracorporeal device 300 is placed in proximity to the pulse generator 110, such as by holding the extracorporeal device 300 close to an implantation site of the pulse generator 110.
  • the neuromodulation unit 104 can further comprise a telemetry unit 120 or telemetry module (e.g., a telemetry hardware module, a telemetry software module, or a combination thereof).
  • the telemetry unit 120 can be configured to analyze the electrophysiological signal detected or recorded by an electrode array by comparing the electrophysiological signal against one or more predetermined signal thresholds or patterns.
  • the neuromodulation unit 104 (or the telemetry unit 120 within the neuromodulation unit 104) can comprise one or more processors and one or more memory units.
  • the one or more processors can be programmed to execute instructions stored in the one or more memory units to compare the electrophysiological signal against one or more predetermined signal thresholds or patterns as part of the analysis.
  • the electrophysiological signal can be a local field potential (LFP) and/or an intracranial/cortical EEG measured within a brain of the subject using any of the electrode arrays (e.g., the first electrode array 102A, the second electrode array 102B, or a combination thereof) implanted endovascularly within the subject.
  • the electrophysiological signal can be an intracranial or cortical electroencephalography (EEG) signal.
  • the electrophysiological signal can be an electrocorticography (ECoG) signal received by the telemetry unit 120 from an ECoG electrode array deployed on a surface of the brain.
  • ECG electrocorticography
  • the ECoG electrode array can be a flexible or stretchable electrode-mesh or one or more electrode patches placed on a surface of the brain.
  • the electrophysiological signal can be a signal indicating a heart rate or change in heart rate of the subject.
  • the electrophysiological signal can be an electrocardiogram (ECG/EKG) signal measured by the neuromodulation unit 104 when the neuromodulation unit 104 is implanted within a pectoral region or implanted within a subclavian space of the subject.
  • the electrophysiological signal can be an EEG signal received by the telemetry unit 120 from a plurality of external electrodes (an external electrode array) placed on a scalp of the subject.
  • the EEG signal can be obtained from a head-mounted EEG monitoring system (e.g., EEG skull cap or EEG-visor).
  • the EEG electrodes can serve as the recording or detecting electrode array.
  • the electrophysiological signal can provide information or data that can be used to predict or indicate whether the subject is about to experience an epileptic seizure.
  • the neuromodulation unit 104 can command the pulse generator 110 to generate an electrical impulse when epileptiform transients or other seizure pre-onset signatures are detected in the EEG signal.
  • the neuromodulation unit 104 (or the telemetry unit 120) can adjust or vary one or more signal thresholds.
  • the neuromodulation unit 104 can also select from different signal thresholds. For example, the neuro modulation unit 104 can raise or lower a signal threshold based on how often the subject experiences a seizure after a signal threshold is met (or not met).
  • the neuromodulation system 100 can be considered to operate in a closed-loop mode or to provide “responsive neurostimulation” when the intracorporeal target is stimulated in response to a detected electrophysiological signal associated or correlated with the onset of epileptic seizures.
  • the system 100 can also classify or stratify the electrophysiological signals detected or recorded into low risk, medium risk, or high risk and only generate the electrical impulse when the signal is considered medium risk or high risk.
  • the neuromodulation unit 104 can be configured to analyze the electrophysiological signal detected or recorded by at least one of the electrode arrays (e.g., any of the first electrode array 102 A, the second electrode array 102B, or a combination thereof) and transmit an electrical impulse to the same electrode array or another electrode array via the pulse generator 110 in response to the electrophysiological signal detected or recorded.
  • the electrode arrays e.g., any of the first electrode array 102 A, the second electrode array 102B, or a combination thereof
  • the electrical impulse can be biphasic, monophasic, sinusoidal, or a combination thereof.
  • the pulse generator 110 can generate the electrical impulse by increasing a current amplitude of the electrical impulse from 0 mA to up to 10 mA in 0.1 mA steps and increasing a voltage of the electrical impulse from 0 V to up to 10 V in 0.25 V steps.
  • the electrical impulse generated can have a pulse width of between 25 pS to about 600 pS.
  • a timing parameter of the electrical impulse can also be adjusted to allow for different stimulation timing patterns.
  • the electrical impulse generated can have a frequency between 1 Hz and 400 Hz.
  • a frequency of the electrical impulse can be set at a low frequency (between about 1 Hz to 10 Hz), a medium frequency (between about 10 Hz to 150 Hz), and a high frequency (between about 150 Hz to 400 Hz).
  • Stimulating the intracorporeal target e.g., the vagus nerve
  • can increase blood flow to key areas of the brain and raise levels of certain neurotransmitters involved in suppressing seizure activity e.g., inhibitory neurotransmitters such as gammaaminobutyric acid (GABA)).
  • GABA gammaaminobutyric acid
  • the neuromodulation system 100 can operate in an open-loop mode or configuration such that the intracorporeal target is stimulated via an electrode array intermittently or periodically based on a pre-set schedule.
  • FIGs. 2A-2D illustrates various other embodiments of endovascular carriers 108 that can be used to carry an electrode array 102 and secure the electrode array 102 to an implantation site within a vasculature of the subject.
  • the endovascular carrier 108 can be an expandable stent or endovascular scaffold comprising an electrode array 102 coupled to the expandable stent or endovascular scaffold.
  • the expandable stent or endovascular scaffold can comprise multiple filaments woven into a tubular-like structure.
  • the stent or scaffold is configured to be self-expandable.
  • the stent or scaffold can self-expand from a collapsed or crimped configuration to an expanded configuration when deployed within a vasculature of the subject.
  • the stent or scaffold can self-expand into a shape or diameter pre-set to fit a particular vein, artery, or another vessel.
  • the stent or scaffold can be expanded by a balloon catheter.
  • the electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to an external boundary or radially outward portion of the expandable stent or scaffold.
  • the electrodes 112 of the electrode array 102 can be arranged along filaments making up the external boundary or radially outward portion of the expandable stent or scaffold (i.e., the part of the stent or scaffold configured to be in contact with the vessel lumen).
  • the filaments of the expandable stent or endovascular scaffold can be made in part of a shape-memory alloy.
  • the filaments of the expandable stent or endovascular scaffold can be made in part of Nitinol (e.g., Nitinol wire).
  • the filaments of the expandable stent or endovascular scaffold can also be made in part of stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, iridium, rhodium, or a combination thereof.
  • the filaments of the expandable stent or endovascular scaffold can also be made in part of a shape memory polymer.
  • the entire carrier and array assembly can be referred to as a stent-electrode array 109.
  • the stent-electrode arrays 109 disclosed herein can be any of the stents, scaffolds, stent-electrodes, or stent-electrode arrays disclosed in U.S. Patent Pub. No. US 2014/0288667; U.S. Patent Pub. No. 2020/0078195; U.S. Patent Pub. No. 2019/0336748;
  • Fig. 2A illustrates another embodiment of the endovascular carrier 108 as a coiled wire 200.
  • the coiled wire 200 can be used in vessels that are too small to accommodate the stent-electrode array 109.
  • the coiled wire 200 can be a biocompatible wire 202 or microwire configured to wind itself into a coiled pattern or a substantially helical pattern.
  • the electrodes 112 of the electrode array 102 can be scattered along a length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to distinct points along a length of the coiled wire 200.
  • the electrodes 112 of the electrode array 102 can be separated from one another such that no two electrodes 112 are within a predetermined separation distance (e.g., at least 10 pm, at least 100 pm, or at least 1.0 mm) from one another.
  • a predetermined separation distance e.g., at least 10 pm, at least 100 pm, or at least 1.0 mm
  • the wire 202 or microwire can be configured to automatically wind itself into a coiled configuration (e.g., helical pattern) when the wire 202 or microwire is deployed out of a delivery catheter.
  • the coiled wire 200 can automatically attain its coiled configuration via shape memory when the delivery catheter or sheath is retracted.
  • the coiled configuration or shape can be a preset or shape memory shape of the wire 202 or microwire prior to the wire 202 or microwire being introduced into a delivery catheter.
  • the preset or pre-trained shape can be made to be larger than the diameter of the anticipated deployment or implantation vessel to enable the radial force exerted by the coils to secure or position the coiled wire 200 in place within the deployment or implantation vessel.
  • the coiled wire 200 can attain the coiled configuration when a pushing force is applied to the wire 202 or microwire to compel or otherwise bias the wire 202 or micro wire into the coiled configuration.
  • the coiled wire 200 can have a wire diameter 204 and a coil diameter 206.
  • the wire diameter 204 can be a diameter of the underlying wire 202 or microwire used to form the endovascular carrier 108. In some embodiments, the wire diameter 204 can be between about 25 pm to about 1.0 mm. In other embodiments, the wire diameter 204 can be between about 100 pm to about 500 pm.
  • the coil diameter 206 can be between 1.0 mm to 15.0 mm. More specifically, the coil diameter 206 can be between about 3.0 mm to about 8.0 mm (e.g., about 6.0 mm or 7.0 mm). In some embodiments, the coil diameter 206 can be between 15.0 mm to about 25.0 mm. The coil diameter 206 can be set based on a diameter of a target vessel or deployment vessel.
  • the wire 202 or microwire can be made in part of a shape-memory alloy, a shape- memory polymer, or a combination thereof. For example, wire 202 or microwire can be made in part of Nitinol (e.g., Nitinol wire).
  • the wire 202 or microwire can also be made in part of stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, iridium, rhodium, or a combination thereof.
  • Fig. 2B illustrates that a first electrode array 102A can be carried by a first coiled wire 200A and a second electrode array 102B can be carried by a second coiled wire 200B connected to the first coiled wire 200A.
  • the first coiled wire 200A can serve as the first endovascular carrier 108A and the second coiled wire 200B can serve as the second endovascular carrier 108B.
  • Each of the first coiled wire 200A and the second coiled wire 200B can be the same as the coiled wire 200 (see Fig. 2A) previously discussed.
  • the first coiled wire 200A can be connected to the second coiled wire 200B by an uncoiled segment of the wire 202 or microwire.
  • the first coiled wire 200A can be connected to the second coiled wire 200B by an uncoiled segment of the same wire 202 or microwire used to make the first coiled wire 200A and the second coiled wire 200B.
  • first coiled wire 200A serving as the first endovascular carrier 108 A and the second coiled wire 200B serving as the second endovascular carrier 108B can be implanted along different segments of the same vessel or implanted within different vessels.
  • the first electrode array 102A carried by the first coiled wire 200A can serve as a recording electrode array and the second electrode array 102B carried by the second coiled wire 200B can serve as the stimulating electrode array.
  • both the first electrode array 102A carried by the first coiled wire 200A and the second electrode array 102B carried by the second coiled wire 200B can serve as the recording electrode arrays and/or the stimulating electrode arrays.
  • Fig. 2C illustrates a further embodiment of the endovascular carrier 108 as an anchored wire 208.
  • the anchored wire 208 can be used in vessels that are too small or too tortuous to accommodate either the coiled wire 200 or the stent-electrode array 109.
  • the anchored wire 208 can comprise a biocompatible wire 202 or microwire attached or otherwise coupled to an anchor or another type of endovascular securement mechanism.
  • Fig. 2C illustrates that the anchored wire 208 can comprise a barbed anchor 210, a radially-expandable anchor 212, or a combination thereof (both the barbed anchor 210 and the radially-expandable anchor 212 are shown in broken or phantom lines in Fig. 2C).
  • the barbed anchor 210 can be positioned at a distal end of the anchored wire 208. In other embodiments, the barbed anchor 210 can be positioned along one or more sides of the wire 202 or microwire. The barbs of the barbed anchor 210 can secure or moor the anchored wire 208 to an implantation site within the subject.
  • the radially-expandable anchor 212 can be a segment of the wire 202 or microwire shaped as a coil or loop.
  • the coil or loop can be sized to allow the coil or loop to conform to a vessel lumen and to expand against a lumen wall to secure the anchored wire 208 to an implantation site within the vessel.
  • the coil or loop can be sized to be larger than the diameter of the anticipated deployment or implantation vessel to enable the radial force exerted by the coil or loop to secure or position the anchored wire 208 in place within the deployment or implantation vessel.
  • the radially-expandable anchor 212 can be positioned at a distal end of the anchored wire 208. In other embodiments, the radially-expandable anchor 212 can be positioned along a segment of the anchored wire 208 proximal to the distal end. [0124]
  • the electrodes 112 of the electrode array 102 can be scattered along a length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be affixed, secured, or otherwise coupled to distinct points along a length of the anchored wire 208.
  • the electrodes 112 of the electrode array 102 can be separated from one another such that no two electrodes 112 are within a predetermined separation distance (e.g., at least 10 pm, at least 100 pm, or at least 1.0 mm) from one another.
  • Fig. 2C illustrates the anchored wire 208 having only one barbed anchor 210 and one radially-expandable anchor 212, it is contemplated by this disclosure that the anchored wire 208 can comprise a plurality of barbed anchors 210 and/or radially-expandable anchors 212.
  • Fig. 2D illustrates an embodiment of an endovascular carrier 214 carrying different electrode arrays 102 (e.g., the first electrode array 102A and the second electrode array 102B). As shown in Fig. 2D, the endovascular carrier 214 can be the stent-electrode array 109 previously discussed.
  • two electrode arrays 102 can be coupled to the same expandable stent or endovascular scaffold. In other embodiments, three or more electrode arrays 102 can be coupled to the same expandable stent or endovascular scaffold.
  • FIG. 2D illustrates the electrodes 112 of the first electrode array 102A using dark circles and the electrodes 112 of the second electrode array 102B using white circles, it should be understood by one of ordinary skill in the art that the difference in color is only for ease of illustration.
  • the electrodes 112 of the first electrode array 102A can be used as dedicated recording or detection electrodes and the electrodes 112 of the second electrode array 102B can be used as dedicated stimulating electrodes. In this manner, only one endovascular carrier is needed to deploy both the recording electrode array and the stimulating electrode array. Moreover, in this embodiment, the electrodes 112 of the first electrode array 102 A can record and communicate via different data or communication channels than electrodes 112 of the second electrode array 102B.
  • FIG. 2D illustrates the endovascular carrier 214 as an expandable stent or scaffold, it is contemplated by this disclosure that any of endovascular carriers disclosed herein, including the coiled wire 200 and the anchored wire 208, can be used as an endovascular carrier for carrying the at least two types of electrode arrays 102.
  • the electrodes 112 of the electrode arrays 102 depicted in Figs. 2A-2D can be made in part of platinum, platinum black, another noble metal, or alloys or composites thereof.
  • the electrodes 112 of the electrode arrays 102 can be made of gold, iridium, palladium, a gold-palladium-rhodium alloy, rhodium, or a combination thereof.
  • the electrodes 112 can be made of a metallic composite with a high charge injection capacity (e.g., a platinum-iridium alloy or composite).
  • the electrodes 112 can be shaped as circular disks having a disk diameter of between about 100 pm to 1.0 mm. In other embodiments, the electrodes 112 can have a disk diameter of between 1.0 mm and 1.5 mm. In additional embodiments, the electrodes 112 can be cylindrical, spherical, cuff-shaped, ring-shaped, partially ring-shaped (e.g., C-shaped), or semi-cylindrical,
  • the electrodes 112 can have their conductive properties enhanced by increasing the surface area of the electrodes 112 through surface roughening with chemical or electrochemical roughening methods or coating with a conductive polymeric coating such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).
  • a conductive polymeric coating such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS).
  • Fig. 3A illustrates that the neuromodulation unit 104 and the endovascular carriers 108 carrying the electrode arrays 102 can be implanted within the subject.
  • the neuromodulation unit 104 can be powered by a portable power supply such as one or more rechargeable batteries.
  • the batteries of the neuromodulation unit 104 can be recharged by an extracorporeal device 300 via electromagnetic induction.
  • the neuromodulation unit 104 can also be activated or powered by the extracorporeal device 300 when the extracorporeal device 300 is placed in proximity to the neuromodulation unit 104 (e.g., when held up next to the implantation site of the neuromodulation unit 104).
  • the neuromodulation unit 104 can comprise a first magnetic component 118 (e.g., a receiving or secondary coil) and the extracorporeal device 300 can comprise a second magnetic component 302 (e.g., a primary or transmission coil) configured to be magnetically coupled to the first magnetic component 118.
  • the extracorporeal device 300 can charge or power the neuromodulation unit 104 via electromagnetic induction.
  • the pulse generator 110 can be a standalone device separate from the neuromodulation unit 104.
  • the pulse generator 110 can also comprise a first magnetic component 118 (e.g., a receiving or secondary coil) configured to be magnetically coupled to a second magnetic component 302 (e.g., a primary or transmission coil) within the extracorporeal device 300.
  • the pulse generator 110 can be charged or powered by the extracorporeal device 300 via electromagnetic induction.
  • any of the endovascular carriers 108 can be implanted within a cortical or cerebral vessel of the subject.
  • an electrode array 102 coupled to a stent-electrode array 109 serving as the endovascular carrier 108 can be implanted within a venous sinus (e.g., a superior sagittal sinus) of the subject.
  • the stent-electrode array 109 can be connected or coupled directly to the neuromodulation unit 104 via its own transmission lead 106 or cable.
  • the stent-electrode array 109 can be coupled to the neuromodulation unit 104 via a shared transmission lead 106 or cable.
  • the stent-electrode array 109 deployed within the venous sinus can be used to detect or record an electrophysiological signal of the subject (i.e., used as a recording electrode array).
  • the stent-electrode array 109 deployed within the venous sinus can be used to stimulate an intracorporeal target (e.g., a motor cortex) of the subject. In this manner, the stent-electrode array 109 deployed within the venous sinus can be used as a stimulating electrode array.
  • the stent-electrode array 109 deployed within the venous sinus can be used as both a recording electrode array and a stimulating electrode array (see, e.g., the stent-electrode array of Fig. 2D).
  • Fig. 3A also illustrates that an electrode array 102 coupled to a coiled wire 200 serving as the endovascular carrier 108 can be implanted within a superficial cerebral vein (e.g., a vein of Trolard) of the subject.
  • the coiled wire 200 can be connected or coupled directly to the neuromodulation unit 104 via its own transmission lead 106 or cable. In other embodiments, the coiled wire 200 can be coupled to the neuromodulation unit 104 via a shared transmission lead 106 or cable.
  • the coiled wire 200 deployed within the superficial cerebral vein can be used to detect or record an electrophysiological signal of the subject (i.e., used as a recording electrode array).
  • the coiled wire 200 deployed within the superficial cerebral vein can be used to stimulate an intracorporeal target (e.g., a motor cortex) of the subject. In this manner, the coiled wire 200 deployed within the superficial cerebral vein can be used as a stimulating electrode array.
  • the coiled wire 200 deployed within the superficial cerebral vein can be used as both a recording electrode array and a stimulating electrode array.
  • Fig. 3A further illustrates that an electrode array 102 coupled to an anchored wire 208 serving as the endovascular carrier 108 can be implanted within a deep cerebral vein (e.g., a superior thalamostriate vein) of the subject.
  • the anchored wire 208 can be connected or coupled directly to the neuromodulation unit 104 via its own transmission lead 106 or cable. In other embodiments, the anchored wire 208 can be coupled to the neuromodulation unit 104 via a shared transmission lead 106 or cable.
  • the anchored wire 208 deployed within the deep cerebral vein can be used to detect or record an electrophysiological signal of the subject (i.e., used as a recording electrode array).
  • the anchored wire 208 deployed within the deep cerebral vein can be used to stimulate an intracorporeal target (e.g., an anterior nucleus of thalamus) of the subject.
  • an intracorporeal target e.g., an anterior nucleus of thalamus
  • the anchored wire 208 deployed within the deep cerebral vein can be used as a stimulating electrode array.
  • the anchored wire 208 deployed within the deep cerebral vein can be used as both a recording electrode array and a stimulating electrode array.
  • Fig. 3A also illustrates that an electrode array 102 coupled to a stent-electrode array 109 serving as the endovascular carrier 108 can be implanted within an internal jugular vein superior to (or above) the jugular foramen of the subject. In some embodiments, the entire stent-electrode array 109 can be implanted in the internal jugular vein superior to the jugular foramen.
  • the stent-electrode array 109 can be implanted in the internal jugular vein superior to the jugular foramen. Implantation of the stent-electrode array 109 superior to the jugular foramen will be discussed in more detail in later sections. [0145] In some embodiments, the stent-electrode array 109 implanted within the internal jugular foramen can be used to stimulate an intracorporeal target (e.g., a superior ganglion of the vagus nerve) of the subject. In this manner, the stent-electrode array 109 implanted within the internal jugular vein can be used as a stimulating electrode array.
  • an intracorporeal target e.g., a superior ganglion of the vagus nerve
  • FIG. 3A further illustrates that an electrode array 102 coupled to an endovascular carrier 108 (e.g., a coiled wire 200, a stent-electrode array 109, or an anchored wire 208,) can be used as a recording electrode array to record an electrophysiological signal indicating a heart rate or change in heart rate (e.g., ictal tachycardia) of the subject.
  • This cardiac signal can be associated or correlated with the onset of epileptic seizures.
  • this electrophysiological signal can be a cardiac arrhythmia known to be associated or correlated with a high-likelihood of epileptic seizure onset.
  • the neuromodulation unit 104 can be implanted inferior to the head and neck of the subject.
  • the neuromodulation unit 104 can be implanted within a pectoral region of the subject (e.g., beneath the pectoralis major muscle).
  • the pulse generator 110 can be part of the neuromodulation unit 104.
  • the pulse generator 110 can be a standalone device separate from the neuromodulation unit 104.
  • the pulse generator 110 can be implanted within a pectoral region of the subject (e.g., beneath the pectoralis major muscle).
  • Fig. 3B illustrates that the neuromodulation unit 104 can be implanted within a forearm of the subject.
  • the neuromodulation system 100 can comprise an extracorporeal device 300 in the form of an armband 308.
  • the implanted neuromodulation unit 104 can comprise a first magnetic component 118 (e.g., a receiving or secondary coil) and the armband 308 can comprise a second magnetic component 302 (e.g., a primary or transmission coil).
  • the armband 308 can charge or power the neuromodulation unit 104 via electromagnetic induction.
  • the pulse generator 110 can be a standalone device separate from the neuromodulation unit 104.
  • the pulse generator 110 can be implanted within the forearm of the subject.
  • the pulse generator 110 can comprise a first magnetic component 118 (e.g., a receiving or secondary coil) and an armband 308, serving as the extracorporeal device 300, can comprise a second magnetic component 302 (e.g., a primary or transmission coil).
  • the armband 308 can charge or power the pulse generator 110 via electromagnetic induction.
  • Fig. 3A also illustrates that the extracorporeal device 300 can also be implemented as a portable handheld device 304, a wand 306, or a wearable device 308 (e.g., bracelet or watch).
  • the extracorporeal device 300 can be used to recharge one or more batteries within the neuromodulation unit 104, the pulse generator 110, or a combination thereof.
  • the extracorporeal device 300 can be used to activate the pulse generator 110 to transmit an electrical impulse to the stimulating electrode array.
  • Figs. 4A-4C illustrate one embodiment of a transmission lead 106 used to connect the electrode array 102 to the neuromodulation unit 104, the pulse generator 110, or a combination thereof.
  • the transmission lead 106 can be used to connect the first electrode array 102 A or the second electrode array 102B to the neuromodulation unit 104, the pulse generator 110, or a combination thereof.
  • the transmission lead 106 can comprise at least one variable length segment 400 in between the endovascular carrier 108 and a transmission segment 402.
  • a segment length 404 of the variable length segment 400 can be adjusted (e.g., shortened or lengthened) after the transmission lead 106 is deployed within a bodily vessel (e.g., vein, artery, or sinus) of the subject.
  • the transmission segment 402 can be a proximal segment of the transmission lead 106 configured to connect or plug in to the neuromodulation unit 104 (e.g., into the header portion 114 of the neuro modulation unit 104).
  • the transmission segment 402 can be made of one or more conductive wires without shape memory.
  • the transmission segment 402 can be made in part of platinum wire or platinum-iridium wire.
  • the transmission segment 402, along with other segments of the transmission lead 106, can be covered by an insulator (e.g., polyurethane) or insulating coating.
  • Figs. 4A-4C illustrate that the variable length segment 400 can be connected or coupled to a proximal end of the endovascular carrier 108.
  • the endovascular carrier 108 can be a coiled wire 200 and the variable length segment 400 can be connected or coupled directly to the proximal end of the coiled wire 200.
  • variable length segment 400 of the transmission lead 106 can be made in part of a shape-memory alloy.
  • the variable length segment 400 of the transmission lead 106 can also be made of a composite material comprising a shape-memory alloy.
  • the variable length segment 400 of the transmission lead 106 can be made in part of Nitinol (e.g., Nitinol wire).
  • the variable length segment 400 of the transmission lead 106 can be made of composite clad wire or a Nitinol wire having a conductive (e.g., gold or platinum) wire core.
  • Fig. 4A illustrates the shape of the coiled wire 200 and the transmission lead 106 when constricted within a delivery catheter or sheath.
  • Fig. 4B illustrates the shape of the coiled wire 200 and the transmission lead 106 when the coiled wire 200 and the transmission lead 106 are deployed out of the delivery catheter or when the delivery catheter or sheath is retracted.
  • variable length segment 400 of the transmission lead 106 can be configured to automatically recover a preset or pretrained shape.
  • the preset or pretrained shape can be a coiled configuration having loosely-wound coils or coils with a larger pitch or less turns than the coils of the coiled wire 200.
  • the variable length segment 400 can automatically attain its loosely coiled configuration via shape memory when a delivery catheter or sheath carrying the variable length segment 400 is retracted.
  • the preset or pretrained shape of the coils formed by the variable length segment 400 can have a coil diameter less or smaller than the diameter of the anticipated deployment or implantation vessel. This ensures that the radial forces exerted by the coils on the vessel lumen walls do not prevent the coils of the variable length segment 400 from shifting, contracting, or expanding within the bodily vessel of the subject. In some instances, this contraction and expansion can allow the segment length 404 of the variable length segment 400 to vary (e.g., shorten or lengthen). For example, the variable length segment 400 can lengthen by pulling on a proximal (or distal) end of the variable length segment 400.
  • variable length segment 400 can be shortened by pushing on a proximal end of the variable length segment 400 when an endovascular carrier 108 coupled to a distal end of the variable length segment 400 is implanted or otherwise secured within a deployment vessel.
  • the variable length segment 400 can also be shortened by pushing on a distal end of the variable length segment 400 when an endovascular carrier 108 coupled to a proximal end of the variable length segment 400 is implanted or otherwise secured within a deployment vessel.
  • variable length segment 400 can attain a coiled configuration when or only when a pushing force is applied to the variable length segment 400 to compel or urge the variable length segment 400 into the coiled configuration.
  • variable length segment 400 can have little or no shape memory and the variable length segment 400 can be a segment of the transmission lead 106 configured to curl up or deform when a pushing force is applied to the variable length segment 400.
  • One technical problem faced by the applicants is how to design an implantable neuromodulation system comprising endovascular carriers connected or coupled by transmission leads when the distance between such endovascular carriers or the distance between such endovascular carriers and an implantable neuromodulation unit or pulse generator differs by patient or treatment regimen. For example, differences in neck and torso lengths among subjects and where such endovascular carriers are implanted within each subject requires a neuromodulation system that can adapt to different sized anatomy and different implantation requirements.
  • One advantage of the neuromodulation system 100 disclosed herein is the unique transmission leads 106 comprising the variable length segment 400 disclosed herein that can allow the neuromodulation system 100 to be adapted to different sized patients and patients with different implantation requirements.
  • the transmission lead 106 can have a lead diameter of between 0.5 mm and 1.5 mm. More specifically, the transmission lead 106 can have a lead diameter of between 0.5 mm and 1.0 mm. [0164] In some embodiments, the transmission lead 106, or segments thereof, can be covered by an insulator or insulating coating. For example, the transmission lead 106, or segments thereof, can be covered by polyurethane or a polyurethane coating.
  • At least a segment of the transmission lead 106 can be a cable comprising multiple conductive wires or transmission wires coupled to the various electrodes 112 of the electrode array 102.
  • the transmission lead 106 can be a stranded cable comprising a plurality of conductive wires twisted and bundled together and covered by an insulator or insulating material.
  • Figs. 5A-5C illustrate an example method of implanting an embodiment of an electrode array 102 (e.g., any of the first electrode array 102A or the second electrode array 102B).
  • the method can be used when an intracorporeal target 500 is close to but not adjacent to a vessel 502 used to deliver or deploy the electrode array 102.
  • an endovascular carrier 108 carrying the electrode array 102 can be deployed out of the delivery catheter 504.
  • the endovascular carrier 108 can be an anchored wire 208 having the electrode array 102 coupled along a segment of a biocompatible wire 202 or microwire (see, also, Fig. 2C).
  • the wire 202 or microwire can comprise a sharp distal end in the form of a penetrating barb 508 or penetrating anchor coupled or detachably coupled to the distal end of the wire 202 or microwire.
  • the penetrating barb 508 or penetrating anchor can allow the wire 202 or microwire to penetrate or create a puncture in the vessel wall 506 to allow the wire 202 or microwire to extend through the vessel wall 506.
  • the wire 202 or microwire can then direct the electrode array 102 closer to the intracorporeal target 500 (e.g., the target nerve or brain region) such that the electrode array 102 is positioned at or in close proximity to the intracorporeal target 500.
  • the intracorporeal target 500 e.g., the target nerve or brain region
  • Fig. 5C illustrates that once the delivery catheter 504 is retracted, a wire segment 510 proximal to the electrode array 102 can automatically take the shape of a coil.
  • the coil shape of the wire segment 510 can be pre-set prior to being introduced into the delivery catheter 504.
  • the wire segment 510 can have a lead diameter of about 1.0 mm (or less than 1.0 mm) and the vessel 502 can have a vessel diameter of about 6.0 mm.
  • the wire segment 510 can take the shape of a coil having a coil diameter of greater than 6.0 mm.
  • the wire segment 510 can self-expand until the coil pushes against the internal vessel walls to secure the wire segment 510 to the internal vessel walls.
  • the wire segment 510 proximal to the electrode array 102 can be used to also secure the endovascular carrier 108. With the wire segment 510 and the electrode array 102 in place, the penetrating barb 508 can be removed by a stylet or other device extending through the delivery catheter 504.
  • Fig. 6 illustrates one embodiment of a method 600 of treating epilepsy.
  • the method 600 can comprise detecting, using a first electrode array 102A, an electrophysiological signal of a subject in step 602.
  • the first electrode array 102A can act as a recording electrode array.
  • the first electrode array 102A can be affixed, secured, otherwise coupled to the first endovascular carrier 108A (e.g., spaced out along a length of the first endovascular carrier 108 A and/or coupled to a radially outer portion of the first endovascular carrier 108A).
  • the first endovascular carrier 108A can be implanted within an artery, vein, or sinus of the subject. Possible implantation sites for the first endovascular carrier 108A will be discussed in more detail in the following sections.
  • the method 600 can also comprise analyzing the electrophysiological signal using a neuromodulation unit 104 implanted within the subject and electrically coupled to the first electrode array 102A via one or more conductive leads and/or a transmission lead 106 in step 604.
  • the neuromodulation unit 104 can be configured to analyze the electrophysiological signal by (i) comparing the signal detected against one or more thresholds (e.g., detecting a spike in the signal), (ii) detecting certain signal patterns or rhythmic activity in specific frequency ranges, (iii) comparing absolute sample-to-sample amplitude differences within a predetermined time window, (iv) measuring a change in signal energy, or a combination thereof.
  • the method 600 can also comprise stimulating an intracorporeal target of the subject using a second electrode array 102B in response to the electrophysiological signal detected in step 606.
  • the second electrode array 102B can act as a stimulating electrode array.
  • the second electrode array 102B can be affixed, secured, or otherwise coupled to the second endovascular carrier 108B (e.g., spaced out along a length of the second endovascular carrier 108B and/or coupled to a radially outer portion of the second endovascular carrier 108B).
  • the second endovascular carrier 108B can be implanted within an artery, vein, or sinus of the subject superior to a base of the skull of the subject.
  • Fig. 7 illustrates another embodiment of a method 700 of treating epilepsy.
  • the method 700 can comprise detecting, using a first electrode array 102A, an electrophysiological signal of a subject in step 702.
  • the first electrode array 102 A can act as a recording electrode array.
  • the first electrode array 102 A can be affixed, secured, otherwise coupled to an endovascular carrier 108 implanted endovascularly within an artery, vein, or sinus of the subject superior to a base of the skull of the subject.
  • the endovascular carrier 108 can be the endovascular carrier 214 depicted in Fig.
  • the first electrode array 102 A can be spaced out along a length of the endovascular carrier 108 and/or coupled to a radially outer portion of the endovascular carrier 108. Possible implantation sites for the endovascular carrier 108 will be discussed in more detail in the following sections.
  • the method 700 can also comprise analyzing the electrophysiological signal using a neuromodulation unit 104 implanted within the subject and electrically coupled to the first electrode array 102A via one or more conductive leads and/or a transmission lead 106 in step 704.
  • the neuromodulation unit 104 can be configured to analyze the electrophysiological signal by (i) comparing the signal detected against one or more thresholds (e.g., detecting a spike in the signal), (ii) detecting certain signal patterns or rhythmic activity in specific frequency ranges, (iii) comparing absolute sample-to-sample amplitude differences within a predetermined time window, (iv) measuring a change in signal energy, or a combination thereof.
  • the method 700 can also comprise stimulating an intracorporeal target of the subject using a second electrode array 102B in response to the electrophysiological signal detected in step 706.
  • the second electrode array 102B can be spaced out along a length of the endovascular carrier 108 and/or coupled to a radially outer portion of the endovascular carrier 108. In this manner, the second electrode array 102B can act as a stimulating electrode array.
  • the second electrode array 102B can be affixed, secured, or otherwise coupled to the same endovascular carrier 108 (e.g., spaced out along a length of the endovascular carrier 108 and/or coupled to a radially outer portion of the endovascular carrier 108).
  • the electrodes of the second electrode array 102B can be separate from the electrodes of the first electrode array 102A.
  • Figs. 6 and 7 disclose methods of treating epilepsy, it is contemplated by this disclosure that the neuromodulation system 100 disclosed herein can also be used in treating other disorders or conditions including headaches, bipolar disorder, obesity, Alzheimer’s disease, Parkinson’s disease, rheumatoid arthritis, or inflammatory bowel disease.
  • a method of treating one of the aforementioned conditions/disorders can comprise detecting, using a first electrode array 102A, an electrophysiological signal of a subject associated with or related to an onset of symptoms related to the condition/disorder.
  • the first electrode array 102 A can be coupled to a first endovascular carrier 108 A implanted superior to a base of the skull of the subject.
  • the method can also comprise analyzing the electrophysiological signal using a neuromodulation unit 104 implanted within the subject and electrically coupled to the first electrode array 102A.
  • the method can further comprise stimulating an intracorporeal target of the subject using a second electrode array 102B in response to the electrophysiological signal detected.
  • the second electrode array 102B can be coupled to a second endovascular carrier 108B implanted endovascularly within the subject and electrically coupled to the neuromodulation unit 104.
  • stimulating the intracorporeal target can comprise generating an electrical impulse using a pulse generator 110 of the neuromodulation unit 104. Stimulating the intracorporeal target can alleviate or lessen a symptom or contributing factor of the condition/disorder.
  • Fig. 8A illustrates that the endovascular carrier 108 (including any of the first endovascular carrier 108A or the second endovascular carrier 108B) can be implanted within the internal jugular vein 800 (e.g., the right internal jugular vein or the left internal jugular vein) superior to a jugular foramen 802 of the subject.
  • the jugular foramen 802 is a cavity formed in the inferior portion of the base of the subject’s skull.
  • the jugular foramen 802 is formed by the petrous part of the temporal bone anteriorly and the occipital bone posteriorly.
  • the electrode array 102 coupled to the endovascular carrier 108 can be used to stimulate a vagus nerve 804 of the subject.
  • the intracorporeal target or stimulation target can be the superior ganglion 806 of the vagus nerve 804. In other embodiments, the intracorporeal target or the stimulation target can be both the superior ganglion 806 and the inferior ganglion 808 of the vagus nerve 804.
  • a method of treating epilepsy can comprise implanting a first electrode array 102A coupled to a first endovascular carrier 108A in a cerebral or cortical vein or sinus of the subject to record an electrophysiological signal of the subject associated or correlated with or indicative of the onset of an epileptic seizure.
  • the method can also comprise implanting a second electrode array 102B coupled to a second endovascular carrier 108B (e.g., the stent-electrode array 109) in the internal jugular vein 800 superior to the jugular foramen 802 to stimulate the vagus nerve 804 of the subject.
  • a neuromodulation unit 104 electrically coupled to the first electrode array 102 A and the second electrode array 102B can analyze the electrophysiological signal and instruct a pulse generator 110 of the neuromodulation unit 104 to generate an electrical impulse to stimulate the vagus nerve 804.
  • the electrical impulse can be biphasic, monophasic, sinusoidal, or a combination thereof.
  • the electrical impulse can be charge-balanced biphasic pulses.
  • the pulse generator 110 can generate the electrical impulse by increasing a current amplitude of the electrical impulse from 0.25 mA to up to 2 mA in 0.1 mA steps and increasing a voltage of the electrical impulse from 0 V to up to 10 V in 0.25 V steps.
  • the electrical impulse generated can have a pulse width of between 250 pS to about 500 pS.
  • a timing parameter of the electrical impulse can also be adjusted to allow for different stimulation timing patterns.
  • the electrical impulse generated can have a frequency between 10 Hz and 30 Hz.
  • At least part of the endovascular carrier 108 can be implanted within the internal jugular vein 800 superior to the jugular foramen 802. In additional embodiments, at least part of the endovascular carrier 108 can be implanted within a branch or tributary of the internal jugular vein 800.
  • the endovascular carrier 108 can be implanted within the internal carotid artery 810 superior to the base of the skull of the subject. In further embodiments, the endovascular carrier 108 can be implanted within the internal carotid artery 810 superior to a carotid foramen 812 of the subject. In other embodiments, at least part of the endovascular carrier 108 can be implanted within the internal carotid artery 810 superior to the base of the skull of the subject. In further embodiments, at least part of the endovascular carrier 108 can be implanted within the internal carotid artery 810 superior to the carotid foramen 812. In these and other embodiments, the intracorporeal target can be the vagus nerve 804 of the subject.
  • Fig. 8A illustrates the endovascular carrier 108 as a stent-electrode array 109
  • any of the endovascular carriers 108 disclosed herein can be implanted within the internal jugular vein 800.
  • any of the endovascular carriers 108 disclosed herein can be implanted within the internal carotid artery 810.
  • FIGs. 8B and 8C illustrate a proximity of the vagus nerve 804 to the internal jugular vein 800.
  • at least part of the vagus nerve 804 extending through the neck and into the skull of the subject is in contact with the internal jugular vein 800 or adjacent to the internal jugular vein 800 (i.e., separated from the internal jugular vein 800 by less than 2.0 mm).
  • Fig. 8B illustrates a partial sectional view of a transverse section of a subject at the level of the C6 vertebra showing the vagus nerve 804 and surrounding vessels, including the internal jugular vein 800.
  • the internal jugular vein 800 can serve as a possible implantation site for an endovascular carrier 108 carrying an electrode array 102 (e.g., a stimulating electrode array).
  • the endovascular carrier 108 can also be implanted within a common carotid artery (outside of the skull of the subject) or an external carotid artery.
  • endovascular carriers 108 implanted in vessels within the neck of the subject can wear down over time as a result of the natural motion of the neck (e.g., bending, flexion, extension, rotation, etc.). Moreover, endovascular carriers 108 implanted in vessels within the neck can also be damaged by external forces applied to the neck of the subject.
  • One advantage of implanting the endovascular carriers 108 within the skull of the subject e.g., in an internal carotid artery superior to a jugular foramen
  • the skull acts as a protective casing for the endovascular carrier 108 and only one or more thin transmission leads 106 extend through the neck of the subject. This can also increase patient comfort and increase the deployed lifespan of the endovascular carrier.
  • electrophysiological recordings taken from electrodes within the skull are less impacted by extraneous signals such as heart beating artifacts.
  • Fig. 9A-9G illustrate certain veins and sinuses of the subject that can serve as implantation sites for the endovascular carriers 108 carrying the electrode arrays 102. Moreover, Figs. 9A-9G also illustrate certain intracorporeal targets or stimulation targets that can be stimulated as part of a treatment for epilepsy or other disorders/conditions.
  • the first endovascular carrier 108A carrying the first electrode array 102A can be implanted within a venous sinus of the subject.
  • the first endovascular carrier 108A carrying the first electrode array 102A can be implanted within a superior sagittal sinus 900, an inferior sagittal sinus 902, a sigmoid sinus 904, a transverse sinus 906, or a straight sinus 908.
  • the first endovascular carrier 108A carrying the first electrode array 102A can be implanted within a superficial cerebral vein of the subject.
  • the first endovascular carrier 108A carrying the first electrode array 102A can be implanted within at least one of a vein of Labbe 910, a vein of Trolard 912, a Sylvian vein 914, and a Rolandic vein 916.
  • the first endovascular carrier 108 A carrying the first electrode array 102 A can also be implanted within a deep cerebral vein of the subject.
  • the first endovascular carrier 108 A carrying the first electrode array 102 A can be implanted within at least one of a vein of Rosenthal 918, a vein of Galen 920, a superior thalamostriate vein 922, an inferior thalamostriate vein 924, and an internal cerebral vein 926.
  • the first endovascular carrier 108A carrying the first electrode array 102A can also be implanted within at least one of a central sulcal vein, a post- central sulcal vein, and a pre-central sulcal vein.
  • the first endovascular carrier 108A can also be implanted or configured to be implanted within a vessel extending through a hippocampus or amygdala of the subject.
  • the first electrode array 102A can be configured to detect or record an electrophysiological signal of the subject associated or correlated with the onset of epileptic seizures.
  • the electrophysiological signal can be a local field potential (LFP) and/or an intracranial/cortical EEG measured within a cerebral or cortical vessel (e.g., a venous sinus or cortical vein).
  • the electrophysiological signal can be an electrocorticography (ECoG) signal.
  • the neuromodulation unit 104 can further comprise a telemetry unit 120 or telemetry module (e.g., a telemetry hardware module, a telemetry software module, or a combination thereof).
  • the telemetry unit 120 can be configured to analyze the electrophysiological signal detected or recorded by the first electrode array 102A.
  • the one or more processors of the neuromodulation unit 104 can be programmed to execute instructions stored in the one or more memory units to analyze the electrophysiological signal by: (i) comparing the signal detected against one or more thresholds (e.g., detecting a spike in the signal), (ii) detecting certain signal patterns or rhythmic activity in specific frequency ranges, (iii) comparing absolute sample-to-sample amplitude differences within a predetermined time window, (iv) measuring a change in signal energy, or a combination thereof.
  • one or more thresholds e.g., detecting a spike in the signal
  • detecting certain signal patterns or rhythmic activity in specific frequency ranges e.g., detecting certain signal patterns or rhythmic activity in specific frequency ranges
  • comparing absolute sample-to-sample amplitude differences within a predetermined time window e.g., comparing absolute sample-to-sample amplitude differences within a predetermined time window
  • measuring a change in signal energy e.g.,
  • the neuromodulation unit 104 can then instruct a pulse generator 110 (e.g., a pulse generator provided as part of the neuromodulation unit 104 or a pulse generator separate from the neuromodulation unit 104) to generate an electrical impulse to stimulate an intracorporeal target or stimulation target via the second electrode array 102B coupled to a second endovascular carrier 108B.
  • a pulse generator 110 e.g., a pulse generator provided as part of the neuromodulation unit 104 or a pulse generator separate from the neuromodulation unit 104 to generate an electrical impulse to stimulate an intracorporeal target or stimulation target via the second electrode array 102B coupled to a second endovascular carrier 108B.
  • the second endovascular carrier 108B can be implanted within an internal jugular vein (either a right internal jugular vein or a left internal jugular vein) or an internal carotid artery.
  • the intracorporeal target or stimulation target can be the cerebellum 928 of the subject.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within at least one of a sigmoid sinus 904 and a straight sinus 908 of the subject.
  • the second endovascular carrier 108B carrying the second electrode array 102B can also be implanted within a transverse sinus 906 of the subject. At least part of the cerebellum 928 is adjacent to the sigmoid sinus 904, the straight sinus 908, and the transverse sinus 906 (i.e., separated by less than 2.0 mm).
  • the intracorporeal target or stimulation target can be the motor cortex 930 of the subject.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within at least one of an inferior sagittal sinus 902, a central sulcal vein, a post-central sulcal vein, and a pre-central sulcal vein of the subject.
  • the second endovascular carrier 108B carrying the second electrode array 102B can also be implanted within a superior sagittal sinus 900 of the subject. At least part of the motor cortex 930 is adjacent to the superior sagittal sinus 900, the central sulcal vein, the post-central sulcal vein, and the pre-central sulcal vein (i.e., separated by less than 2.0 mm).
  • the motor cortex 930 is between about 5.0 mm to about 10.0 mm from the inferior sagittal sinus 902.
  • the intracorporeal target stimulated can also include a fomix 944 of the subject.
  • the fornix 944 can be between about 10.0 mm to about 15.0 mm from the inferior sagittal sinus 902.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within a superficial cerebral vein.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within at least one of a vein of Labbe 910, a vein of Trolard 912, a Sylvian vein 914, and a Rolandic vein 916.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within a deep cerebral vein.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be implanted within at least one of a vein of Rosenthal 918, a vein of Galen 920, a superior thalamostriate vein 922, and an internal cerebral vein 926.
  • the intracorporeal target stimulated can include at least one of the cerebellum 928, the anterior nucleus of thalamus 932, the centromedian nucleus of thalamus 934, the hippocampus 936, the subthalamic nucleus 938, and the caudal zone incerta 940.
  • the vein of Rosenthal 918 can be between about 10.0 mm to about 15.0 mm from at least part of the cerebellum 928, the anterior nucleus of thalamus 932, and the centromedian nucleus of thalamus 934.
  • the vein of Rosenthal 918 can be between about 5.0 mm to about 10.0 mm from at least part of the hippocampus 936, the subthalamic nucleus 938, and the caudal zone incerta 940.
  • the intracorporeal target stimulated can include at least one of the anterior nucleus of thalamus 932, the centromedian nucleus of thalamus 934, the hypothalamus 942, the fornix 944, and the caudal zone incerta 940.
  • the internal cerebral vein 926 can be between about 10.0 mm to about 15.0 mm from at least part of the hypothalamus 942 and the caudal zone incerta 940.
  • the internal cerebral vein 926 can be between about 5.0 mm to about 10.0 mm from at least part of the anterior nucleus of thalamus 932.
  • the internal cerebral vein 926 can be between about 2.0 mm to about 5.0 mm from at least part of the fomix 944.
  • the internal cerebral vein 926 can be adjacent to (i.e., separated by less than 2.0 mm from) the centromedian nucleus of thalamus 934.
  • the intracorporeal target stimulated can include at least one of the anterior nucleus of thalamus 932, the centromedian nucleus of thalamus 934, and the fornix 944.
  • the superior thalamostriate vein 922 can be adjacent to (i.e., separated by less than 2.0 mm from) the anterior nucleus of thalamus 932, the centromedian nucleus of thalamus 934, and the fornix 944.
  • the second endovascular carrier 108B carrying the second electrode array 102B can also be implanted or configured to be implanted within a vessel extending through a hippocampus or amygdala of the subject.
  • stimulating the intracorporeal target or the stimulation target via the second electrode array 102B can increase blood flow to the intracorporeal target or raise levels of certain neurotransmitters involved in suppressing seizure activity.
  • stimulating the intracorporeal target via the second electrode array 102B can also lead to sodium-channel inactivation (using high-frequency stimulation), long-term depression of certain neurotransmitters (using high-frequency stimulation), and/or glutamatergic depression (using both low-frequency and high-frequency stimulation).
  • the electrical impulse when stimulating cortical or cerebral targets, can be bipolar with the voltage of the electrical impulse increased from IV to 7 V in 0.25 V steps.
  • the electrical impulse generated can have a pulse width of between 90 pS to about 540 pS, a frequency between about 3Hz to 5Hz in a low-frequency range, and a frequency between about 50 Hz to 130 Hz in a high-frequency range.
  • the same endovascular carrier can carry both the first electrode array 102A and the second electrode array 102B.
  • an expandable stent or scaffold can carry both recording electrode arrays and stimulating electrode arrays on the same expandable stent or scaffold.
  • Fig. 10 illustrates one embodiment of a method of deploying or delivering the endovascular carriers 108 (e.g., the first endovascular carrier 108A and the second endovascular carrier 108B) to their respective implantation sites.
  • the figures illustrate two endovascular carriers 108 being deployed, it is contemplated by this disclosure that similar apparatus or similar methods can also be used to deliver a singular endovascular carrier (see, e.g., endovascular carrier 214 of Fig. 2D) carrying separate electrode arrays 102 or three or more endovascular carriers.
  • a first delivery catheter 1000 can be deployed through a jugular incision to the superior sagittal sinus 900.
  • the first delivery catheter 1000 can be deployed under angiographic guidance.
  • the superior sagittal sinus 900 is shown in the figures, it should be understood by one of ordinary skill in the art that the catheter and carriers can be deployed into any vein, sinus, or artery of the subject.
  • a first endovascular carrier 108A carrying a first electrode array 102A can be deployed or otherwise delivered through the first delivery catheter 1000.
  • the first endovascular carrier 108A can be a stent-electrode array 109 configured to self expand into position within the superior sagittal sinus 900.
  • the first electrode array 102A coupled to the first endovascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array or both a recording electrode array and a stimulating electrode array.
  • the first delivery catheter 1000 can be removed from the vasculature of the subject.
  • Fig. 10 also illustrates that a second delivery catheter 1002 can be deployed through the same jugular incision to the internal cerebral vein 926 overlying the anterior nucleus of thalamus 932.
  • the second delivery catheter 1002 can be deployed under angiographic guidance.
  • a second endovascular carrier 108B carrying a second electrode array 102B can be deployed or otherwise delivered through the second delivery catheter 1002.
  • the second endovascular carrier 108B can be a stent- electrode array 109 configured to self expand into position within the internal cerebral vein 926.
  • the second electrode array 102B coupled to the second endovascular carrier 108B can be used as a stimulating electrode array. In other embodiments, the second electrode array 102B can be used as a recording electrode array or both a stimulating electrode array and a recording electrode array.
  • the second delivery catheter 1002 can be removed from the vasculature of the subject.
  • a first transmission lead 106A coupled to the first electrode array 102A on the first endovascular carrier 108A can extend through the neck of the subject (e.g., through a jugular vein) and a proximal end of the first transmission lead 106A can be inserted into a neuromodulation unit 104 (e.g., into a header portion 114, see, Fig. 1) implanted within the subject.
  • a second transmission lead 106B coupled to the second electrode array 102B on the second endovascular carrier 108B can extend through the neck of the subject and a proximal end of the second transmission lead 106B can be inserted into the neuromodulation unit 104.
  • Fig. 11 illustrates another embodiment of a method of deploying or delivering the endovascular carriers 108 (e.g., the first endovascular carrier 108A and the second endovascular carrier 108B) to their respective implantation sites.
  • the figures illustrate two endovascular carriers 108 being deployed, it is contemplated by this disclosure that similar apparatus or similar methods can also be used to deliver a singular endovascular carrier (see, e.g., endovascular carrier 214 of Fig. 2D) carrying separate electrode arrays 102 or three or more endovascular carriers.
  • a first delivery catheter 1100 can be deployed through a jugular incision to the superior sagittal sinus 900.
  • the first delivery catheter 1100 can be deployed under angiographic guidance.
  • the superior sagittal sinus 900 is shown in the figures, it should be understood by one of ordinary skill in the art that the catheter and carriers can be deployed into any vein, sinus, or artery of the subject.
  • a first endovascular carrier 108A carrying a first electrode array 102A (not shown in Fig. 11, see Fig. 1) can be deployed or otherwise delivered through the first delivery catheter 1100.
  • the first endovascular carrier 108A can be a stent-electrode array 109 configured to self expand into position within the superior sagittal sinus 900.
  • the first electrode array 102A coupled to the first endovascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array or both a recording electrode array and a stimulating electrode array.
  • the first delivery catheter 1000 can be removed from the vasculature of the subject.
  • Fig. 11 also illustrates that the first delivery catheter 1100 can be retracted proximally and a second delivery catheter 1102 can be deployed through the retracted first delivery catheter 1100.
  • the second delivery catheter 1002 can be deployed to the internal cerebral vein 926 overlying the anterior nucleus of thalamus 932.
  • the second delivery catheter 1002 can be deployed under angiographic guidance.
  • a second endovascular carrier 108B carrying a second electrode array 102B can be deployed or otherwise delivered through the second delivery catheter 1002.
  • the second endovascular carrier 108B can be a stent- electrode array 109 configured to self expand into position within the internal cerebral vein 926.
  • the second electrode array 102B coupled to the second endovascular carrier 108B can be used as a stimulating electrode array. In other embodiments, the second electrode array 102B can be used as a recording electrode array or both a stimulating electrode array and a recording electrode array.
  • the second delivery catheter 1102 can be removed from the vasculature of the subject.
  • a first transmission lead 106 A coupled to the first electrode array 102 A on the first endovascular carrier 108A can extend through the neck of the subject (e.g., through a jugular vein) and a proximal end of the first transmission lead 106A can be inserted into a neuromodulation unit 104 (e.g., into a header portion 114, see, Fig. 1) implanted within the subject.
  • a second transmission lead 106B coupled to the second electrode array 102B on the second endovascular carrier 108B can extend through the neck of the subject and a proximal end of the second transmission lead 106B can be inserted into the neuromodulation unit 104.
  • FIG. 12 illustrates another embodiment of a method of deploying or delivering the endovascular carriers 108 (e.g., the first endovascular carrier 108A and the second endovascular carrier 108B) to their respective implantation sites.
  • the endovascular carriers 108 e.g., the first endovascular carrier 108A and the second endovascular carrier 108B
  • the figures illustrate two endovascular carriers 108 being deployed, it is contemplated by this disclosure that similar apparatus or similar methods can also be used to deliver three or more endovascular carriers.
  • a delivery catheter 1200 can be deployed through a jugular incision to the superior sagittal sinus 900 and then continuing on to the internal cerebral vein 926 overlying the anterior nucleus of thalamus 932.
  • the delivery catheter 1200 can be deployed under angiographic guidance.
  • the catheter and carriers can be deployed into any vein, sinus, or artery of the subject.
  • the second endovascular carrier 108B carrying the second electrode array 102B can be deployed or otherwise delivered through the delivery catheter 1200.
  • the second endovascular carrier 108B can be a stent-electrode array 109 configured to self expand into position within the internal cerebral vein 926.
  • the second electrode array 102B coupled to the second endovascular carrier 108B can be used as a recording electrode array. In other embodiments, the second electrode array 102B can be used as a stimulating electrode array or both a recording electrode array and a stimulating electrode array.
  • the delivery catheter 1200 can be retracted until the distal end of the delivery catheter 1200 is in place to deploy the first endovascular carrier 108 A into the superior sagittal sinus 900 of the subject.
  • the first endovascular carrier 108A can carry the first electrode array 102A (not shown in Fig. 12, see Fig. 1).
  • the first endovascular carrier 108A can be a stent-electrode array 109 configured to self expand into position within the superior sagittal sinus 900.
  • the first electrode array 102A coupled to the first endovascular carrier 108A can be used as a stimulating electrode array. In other embodiments, the first electrode array 102A can be used as a recording electrode array or both a stimulating electrode array and a recording electrode array.
  • the delivery catheter 1200 can be removed from the vasculature of the subject. [0231] Retracting the delivery catheter 1200 can expose a singular transmission lead 106 connecting the first endovascular carrier 108A to the second endovascular carrier 108B.
  • the singular transmission lead 106 can extend through the neck of the subject (e.g., through a jugular vein) and a proximal end of the transmission lead 106 can be inserted into a neuromodulation unit 104 (e.g., into a header portion 114, see, Fig. 1) implanted within the subject.
  • a neuromodulation unit 104 e.g., into a header portion 114, see, Fig. 1 implanted within the subject.
  • Fig. 13 illustrates an embodiment of a delivery catheter 1300 comprising a first endovascular carrier 108A and a second endovascular carrier 108B connected by a bifurcated transmission lead 1302.
  • a first branch 1304 of the bifurcated transmission lead 1302 can be connected or coupled to the first endovascular carrier 108A and a second branch 1306 of the bifurcated transmission lead 1302 can be connected or coupled to the second endovascular carrier 108B.
  • At least one guidewire 1308 can extend alongside at least one of the branches of the bifurcated transmission lead 1302.
  • the guidewire 1308 can extend through a lumen of one of the endovascular carriers 108 (e.g., the second endovascular carrier 108B) and be detachably coupled to a tip 1310 of the endovascular carrier 108.
  • Another method of deploying or delivering the endovascular carriers 108 can comprise deploying the delivery catheter 1300 through a jugular incision to the superior sagittal sinus 900.
  • the delivery catheter 1300 can be deployed under angiographic guidance.
  • a first endovascular carrier 108A carrying a first electrode array 102A can be deployed or otherwise delivered through the delivery catheter 1300.
  • the first endovascular carrier 108A can be a stent-electrode array 109 configured to self expand into position within the superior sagittal sinus 900.
  • the first electrode array 102A coupled to the first endovascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array or both a recording electrode array and a stimulating electrode array.
  • the delivery catheter 1300 can be retracted proximally and a second endovascular carrier 108B carrying a second electrode array 102B (not shown in Fig. 13, see Fig. 1) can be deployed through the retracted delivery catheter 1300 into a second implantation site (e.g., the internal cerebral vein 926 overlying the anterior nucleus of thalamus 932 of the subject).
  • the guidewire 1308 can be used to guide the second endovascular carrier 108 into place within the second implantation site.
  • the second endovascular carrier 108B can be a stent-electrode array 109 configured to self expand into position within a deployed vessel such as the internal cerebral vein 926.
  • the second electrode array 102B coupled to the second endovascular carrier 108B can be used as a stimulating electrode array.
  • the second electrode array 102B can be used as a recording electrode array or both a stimulating electrode array and a recording electrode array.
  • Retracting the delivery catheter 1300 can expose the bifurcated transmission lead 1302 connecting the first endovascular carrier 108A to the second endovascular carrier 108B.
  • the transmission lead 1302 can extend through the neck of the subject (e.g., through a jugular vein) and a proximal end of the transmission lead 1302 can be inserted into a neuromodulation unit 104 (e.g., into a header portion 114, see, Fig. 1) implanted within the subject.
  • One technical advantage of the closed-loop neuromodulation system 100 disclosed herein is that the system 100 can be delivered through a minimally invasive procedure, via angiography, to a vessel near an intracorporeal/stimulation target (e.g., the vagus nerve) without physically contacting or potentially causing damage to the intracorporeal/stimulation target (e.g., causing damage to the vagus nerve).
  • an intracorporeal/stimulation target e.g., the vagus nerve
  • Another technical advantage of the neuromodulation system 100 disclosed herein is that when the first endovascular carrier 108A (carrying the first electrode array 102A or the recording electrode array) is implanted within a cortical/cerebral vein or sinus and the second endovascular carrier 108B (carrying the second electrode array 10B or the stimulating electrode array) is implanted within a cortical/cerebral vein or sinus or within a vein or artery superior to the skull of the subject, the skull of the subject can act as a protective casing that protects the carriers from potentially destructive external forces and improves the electrophysiological signals detected or recorded.
  • Yet another technical advantage of the neuromodulation system 100 disclosed herein is that the system 100 can provide a closed-loop or responsive stimulation whereby an electrophysiological signal from the subject is detected or otherwise acquired and used as the impetus to trigger the electrical stimulation.
  • An added advantage of the system operating in a closed-loop or responsive mode is that the battery life of the various electronic components of the system can be extended such that such electronic components are only activated when a seizure is imminent or when the subject is observed to be in a high seizure risk state.
  • any components or parts of any apparatus or systems described in this disclosure or depicted in the figures may be removed, eliminated, or omitted to achieve the desired results.
  • certain components or parts of the systems, devices, or apparatus shown or described herein have been omitted for the sake of succinctness and clarity.
  • references to the phrase “at least one of’, when such phrase modifies a plurality of items or components (or an enumerated list of items or components) means any combination of one or more of those items or components.
  • the phrase “at least one of A, B, and C” means: (i) A; (ii) B; (iii) C; (iv) A, B, and C; (v) A and B; (vi) B and C; or (vii) A and C.
  • the term “comprising” and its derivatives, as used herein, are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps.
  • the foregoing also applies to words having similar meanings such as the terms, “including”, “having” and their derivatives.
  • the terms “part,” “section,” “portion,” “member” “element,” or “component” when used in the singular can have the dual meaning of a single part or a plurality of parts.
  • the following directional terms “forward, rearward, above, downward, vertical, horizontal, below, transverse, laterally, and vertically” as well as any other similar directional terms refer to those positions of a device or piece of equipment or those directions of the device or piece of equipment being translated or moved.
  • terms of degree such as “substantially”, “about” and “approximately” as used herein mean the specified value or the specified value and a reasonable amount of deviation from the specified value (e.g., a deviation of up to ⁇ 0.1%, ⁇ 1%, ⁇ 5%, or ⁇ 10%, as such variations are appropriate) such that the end result is not significantly or materially changed.
  • “about 1.0 cm” can be interpreted to mean “1.0 cm” or between “0.9 cm and 1.1 cm.”
  • degrees such as “about” or “approximately” are used to refer to numbers or values that are part of a range, the term can be used to modify both the minimum and maximum numbers or values.

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